FDA approves new indication for Alimta + Keytruda combination for initial treatment of patients with metastatic nonsquamous NSCLC, irrespective of PD-L1 expression status.- Eli Lilly + Merck Inc.

Eli Lilly and Company announced that the FDA has granted approval for a new indication for Alimta (pemetrexed for injection) in combination with carboplatin and Keytruda (pembrolizumab) for the initial treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), irrespective of PD-L1 expression status. Under the FDA's accelerated approval regulations, this indication is approved based on tumor response rate and progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Merck (known as MSD outside the U.S. and Canada) received accelerated approval for the combination of pembrolizumab with Alimta and carboplatin in May 2017. This is the first and only combination of chemotherapy and immunotherapy to earn FDA approval for the first-line treatment of metastatic nonsquamous NSCLC.

This indication, now included in the Alimta prescribing information, is based on data from Merck's KEYNOTE-021 study, Cohort G1. The KEYNOTE-021, Part 2, Cohort G1, study included 123 previously untreated patients with locally advanced or metastatic nonsquamous NSCLC with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations and irrespective of Alimta and carboplatin with pembrolizumab (n=60) demonstrated a statistically significant improvement in objective response rate (ORR) versus Alimta plus carboplatin alone (n=63) (55% vs 29%; all responses were partial) (estimated difference, 26%; 95% confidence interval [CI], range of 42-68 for triplet and range of 18-41 for Alimta plus carboplatin; P=0.0032), and PFS (HR=0.53; 95% CI, 0.31-0.91, P=0.0205). Median PFS was 13.0 months for triplet and 8.9 months for Alimta plus carboplatin (range of 8.3-NE for triplet and 4.4-10.3 for Alimta plus carboplatin).

The labeling for ALIMTA contains warnings and precautions for myelosuppression and increased risk of myelosuppression without vitamin supplementation, renal failure, bullous and exfoliative skin toxicity, interstitial pneumonitis, radiation recall, increased risk of toxicity with ibuprofen in patients with renal impairment and also embryo-fetal toxicity.

Comment: Merck received accelerated approval for the combination of pembrolizumab with Alimta and carboplatin in May 2017. This is the first and only combination of chemotherapy and immunotherapy to earn FDA approval for the first-line treatment of metastatic nonsquamous NSCLC.